Anti-Chol-1 Antigen, GQ1bα, Antibodies Are Associated with Alzheimer’s Disease

Toshio Ariga,Makoto Nakane,Kenji Oguro,Robert K Yu,Masaru Kubota,Susumu Ando,Hemachandra Reddy

doi:10.1371/journal.pone.0063326

Abstract

The interaction of amyloid β-proteins (Aβ) with membrane gangliosides has been reported to be an early event in Aβ fibril formation in Alzheimer’s disease (AD). Neuronal degeneration in AD has been postulated to be associated with the presence of anti-ganglioside antibodies in patient sera. Using an enzyme-linked immunosorbent assay (ELISA) and high-performance thin-layer chromatography (HPTLC) immunostaining, sera from 27 individuals (10 with AD, 6 with vascular dementia (VD), and 11 non-demented age-matched pathological controls) were examined in order to detect anti-glycosphingolipid (GSL) antibodies, including anti-cholinergic-specific antigen (Chol-1α; GQ1bα) antibodies. All sera had natural antibodies against ganglio-N-tetraosyl gangliosides (brain-type gangliosides). However, sera of demented patients with AD and VD had significantly higher titers of anti-GSL antibodies than those in age-matched pathological controls. Although most serum antibodies, including anti- GM1, -GT1b, -GQ1b, -GQ1bα, were of the IgM type, the presence of the IgG type antibodies was also significantly elevated in the sera of demented patients with AD. Anti-GT1b antibodies of the IgG type were elevated in AD (90%, 9 of 10 cases) and VD (100%), respectively. Most surprisingly, anti-GQ1bα antibodies (IgM) were found in 90% (9/10) and 100% (6/6) in the sera of patients with AD and VD, respectively. Since GQ1bα is present in the cerebral cortex and hippocampus, the presence of anti-GQ1bα antibodies may play an important role in disrupting cholinergic synaptic transmission and may participate in the pathogenesis of dementia. We conclude that elevated anti-GSL antibody titers may be useful as an aid for clinical diagnosis of those dementias.

Highlights

Alzheimer’s disease (AD) is the most common type of dementia with clinical symptoms that include abnormalities with memory, judgment, and thinking
Diagnosis of AD and Vascular dementia (VD) was based on criteria of the DSM-IV and Mini-Mental State Examination (MMSE)
It has been hypothesized that serum antibodies are involved in the pathogenesis of AD and certain related diseases

Summary

Introduction

Alzheimer’s disease (AD) is the most common type of dementia with clinical symptoms that include abnormalities with memory, judgment, and thinking. The disease affects more women than men [1,2,3]. Vascular dementia (VD) or multi-infarct dementia is a degenerative cerebrovascular disease and refers to dementia associated with problems in cerebral blood flow. It occurs when the blood supply carrying oxygen and nutrients such as glucose to the brain is interrupted by an occlusion of the cerebrovascular system. Like AD, VD affects memory, thinking, language, judgment, and behavior. These symptoms may be tempered with appropriate medications, but there is no cure for these forms of dementia

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